Progress Towards Engineered Extracellular Matrix
Tissue engineers cannot yet construct sufficiently complex extracellular matrix structures with the correct mechanical and other properties to support the growth of entire organs from scratch. This is why the use of decellularized organs is one line of development, providing a donor extracellular matrix scaffold that can be repopulated with the recipient's cells. This news release is an example of the present state of the art in progress towards building sections of extracellular matrix:
Imitation may be the sincerest form of flattery but the best way to make something is often to co-opt the original process and make it work for you. In a sense, that's how scientists accomplished a new advance in tissue engineering. The team reports culturing cells to make extracellular matrix (ECM) of two types and five different alignments with the strength found in natural tissue and without using any artificial chemicals that could make it incompatible to implant. ECM is the fibrous material between cells in tissues like skin, cartilage, or tendon that gives them their strength, stretchiness, squishiness, and other mechanical properties. To help patients heal wounds and injuries, engineers and physicians have strived to make ECM in the lab that's aligned as well as it is when cells make it in the body. So far, though, they've struggled to recreate ECM. Using artificial materials provides strength, but those don't interact well with the body. Attempts to extract and build upon natural ECM have yielded material that's too weak to reimplant.The team tried a different approach to making both collagen, which is strong, and elastin, which is stretchy, with different alignments of their fibers. They cultured ECM-making cells in specially designed molds that promoted the cells to make their own natural but precisely guided ECM. The strategy built on the insight that when cells clump together and grow in culture, they pull on each other and communicate as they would in the body. The molds therefore were made from agarose so that cells wouldn't stick to the sides or bottom. Instead they huddled together.
To guide ECM growth in particular alignments, the researchers used molds with very specific shapes, often constrained by pegs the cells had to grow around. For instance, to make a rod with collagen fibers aligned along its length (like a tendon) they cultured chondrocyte cells in a dog bone-shaped mold with loops on either end. To make a skin-like "trampoline" of elastin, where the ECM fibers run in all directions, they cultured fibroblast cells to grow in an open area suspended at the center of a honeycomb shape. After the researchers grew various forms of ECM, they did some stress testing. They took the dog bone-shaped tissues made precise measurements of the tissue strength under the force of being pulled apart. The measurements confirmed the self-assembled tissue was about as strong as that found in some of the body's tissues, such as skin, cartilage or blood vessels.